This invention is directed to processes for preparing haloamines and aminoalkylorganometallic compounds.
Haloamines of the general formula R1R2Nxe2x80x94(CH2)nxe2x80x94X (wherein X is halide) can be used for a variety of organic synthesis applications, such as precursors for functionalized amine initiators (U.S. Pat. No. 5,496,940) or as electrophiles for functionalization of polymers (Ueda, Hirao, and Nakahama, Macromolecules, 23, 939-945 (1990)).
Some common literature synthetic methods for the preparation of haloamines involve the chlorination of an omega-amino alcohol with thionylchloride (Leonard and Durand, J. Org. Chem., 33, 1330 (1968), as represented below by Equation 1:
Equation 1:
R1R2Nxe2x80x94(CH2)nxe2x80x94OH+SOCl2xe2x86x92R1R2Nxe2x80x94(CH2)nxe2x80x94Cl
Haloamines can also be prepared by the reaction of an omega-haloalcohol with an amine, as reported in Czech Patent CS 248547 B1 880701, represented below by Equation 2:
Equation 2:
R1R2Nxe2x80x94H+Clxe2x80x94(CH2)nxe2x80x94OHxe2x86x92R1R2Nxe2x80x94(CH2)nxe2x80x94Cl
These methods, however, can require very expensive raw materials and are typically inconvenient, due to the lack of availability of these raw materials, the omega-amino- and halo-alcohols.
U.S. Pat. No. 5,496,940 reports another method for preparing haloamines by the reaction of a lithium amide with the alkylhalide to form the haloamine, represented by Equation 3 below.
Equation 3:
R1R2Nxe2x80x94Li+Brxe2x80x94(CH2)nxe2x80x94Clxe2x86x92R1R2Nxe2x80x94(CH2)nxe2x80x94Cl+LiBr
This method, however, is also expensive. Further, there can be safety concerns associated with this method due to the employment of lithium-based reagents.
Haloamines such as those prepared as described above are useful for a variety of organic synthesis applications. For example, U.S. Pat. No. 5,496,940 reports a process for the preparation of aminoalkyllithium compounds by reacting a haloamine with two or more equivalents of an alkyllithium reagent, such as tert-butyllithium, in a solvent preferably at a temperature less than 38xc2x0 C. An exemplary reaction is set forth below by Equation 4:
Equation 4: 
Monofunctional anionic initiators possessing amine functionalities are useful in preparing amino-terminated styrene-butadiene rubbers (SBRs). See European Patent Application 593049A1 and U.S. Pat. No. 5,496,940. These elastomers have been shown to possess increased rebound, decreased rolling resistance, and lower heat build-up (reduced hysteresis). They are useful in forming improved, energy efficient tires, power belts, and mechanical goods.
The present invention provides processes for preparing haloamines, which can avoid the economic and safety issues associated with prior procedures. In this aspect of the invention, haloamines are prepared by reacting an amine directly with an xcex1,xcfx89-dihaloalkane or an xcex1,xcfx89-dihaloalkene, optionally in the presence of an inorganic or organic acid acceptor, and optionally in a solvent. These haloamines can be prepared from inexpensive, readily available raw materials, namely, xcex1,xcfx89-dihaloalkanes and xcex1,xcfx89-dihaloalkenes and the corresponding amine.
The present invention also provides processes for the synthesis of aminoalkylorganometallic compounds. In this aspect of the invention, alkali metal, such as lithium, is reacted with a suitable haloamine, exclusively, in a hydrocarbon solvent to produce alkylalkali metal compounds containing tertiary amines. Because alkali metal, and not alkylorganometallic compounds, is used in the metallation of the haloamine, the processes of the invention can offer cost savings and safety improvements. In addition, unexpectedly, consistently higher yields can be obtained when the halogen-metal exchange reaction is conducted at elevated temperatures ( greater than 45xc2x0 C.). Less unreacted starting material can also be present when the halogen-metal exchange is conducted at elevated temperatures. Still further, the Wurtz coupling by-product, for example, as illustrated by Equation 5, can be minimized when the halogen-metal exchange is conducted at elevated temperatures.
Equation 5: 
In addition, initiation of the metal-halogen exchange can be very consistent at the elevated temperatures. This consistent initiation can increase the safety of this process, in contrast to the methods detailed in the prior art.
In one aspect of the invention, haloamines of the formula R1R2Nxe2x80x94R3X2 (I) (singly and mixtures) can be prepared, wherein:
R1 and R2 are independently chiral or achiral and independently selected from the group consisting of hydrogen; saturated or unsaturated, linear or branched, C1 to C16 alkyl; saturated or unsaturated C3-C16 cycloalkyl; saturated or unsaturated, linear or branched, silyl-, amino- or oxy-substituted C1-C16 alkyl; saturated or unsaturated silyl-, amino- or oxy-substituted C3-C16 cycloalkyl; saturated or unsaturated, linear or branched, substituted C1-C16 alkyl containing saturated or unsaturated linear or branched C1 to C8 lower alkyl, C3-C16 cycloalkyl, C3-C10 aryl, or substituted aryl containing saturated or unsaturated linear or branched C1-C8 lower alkyl or C3-C8 cycloalkyl; saturated or unsaturated substituted C3-C16 cycloalkyl containing saturated or unsaturated linear or branched C1-C8 lower alkyl, C3-C8 cycloalkyl, C3-C10 aryl, or substituted aryl containing saturated or unsaturated linear or branched C1-C8 lower alkyl or C3-C8 cycloalkyl; or R1 and R2 together may represent a C4-C16 alkylene R4
which alkylene may be saturated or unsaturated, optionally substituted with silyl, amino, or oxygen, or optionally substituted with saturated or unsaturated linear or branched C1-C8 alkyl, C3-C8 cycloalkyl, C3-C10 aryl, or substituted aryl containing saturated or unsaturated linear or branched C1-C8 lower alkyl or C3-C8 cycloalkyl;
R3 is selected from the group consisting of saturated or unsaturated, linear or branched, C3-C25 alkyl; saturated or unsaturated C3-C25 cycloalkyl; saturated or unsaturated, linear or branched, substituted C3-C25 alkyl containing saturated or unsaturated linear or branched C1-C8 alkyl, C3-C8 cycloalkyl, C3-C10 aryl, or substituted aryl containing saturated or unsaturated linear or branched C1-C8 alkyl or C3-C8 cycloalkyl; saturated or unsaturated substituted C3-C25 cycloalkyl containing saturated or unsaturated linear or branched C1-C8 alkyl, C3-C8 cycloalkyl, C3-C10 aryl, or substituted aryl containing saturated or unsaturated linear or branched C1-C8 alkyl or C3-C8 cycloalkyl; and
X2 is halogen, such as chlorine and bromine.
Haloamines of Formula I can be prepared as illustrated below:
R1R2Nxe2x80x94H+X1R3X2xe2x86x92R1R2Nxe2x80x94R3X2+HX1
wherein R1, R2, R3 and X2 are the same as defined above, and X1 is also halogen which may be the same or different as X2.
Exemplary xcex1,xcfx89-dihaloalkanes and xcex1,xcfx89-dihaloalkenes include, but are not limited to, 1-bromo-3-chloro-propane, 1-bromo-4-chloro-butane, 1-bromo-5-chloro-pentane, 1-bromo-6-chloro-hexane, 1-bromo-8-chloro-octane, 1,4-dichloro-2-butene, 1,3-dibromopropane, 1,3-dichloropropane, 1,4-dibromobutane, 1,4-dichlorobutane, 1-bromo-3-chloro-2-methylpropane, 1,3-dibromo-2-methylpropane, 1,3-dichloro-2-methylpropane, 1,3-dichloro-2,2-dimethylpropane, 1,3-dibromo-2,2-dimethylpropane, 1-bromo-3-chloro-2,2-methylpropane, and the like, and mixtures thereof.
Examples of suitable amines useful in this invention include, but are not limited to, t-butyl amine, hexamethyleneimine, 1-methyl-1,4-diaza-cycloheptane (1-methylhomopiperazine), piperidine, pyrrolidine, ethyl amine, dimethyl amine, morpholine, 1-methyl piperazine, and the like, and mixtures thereof.
An inorganic or organic acid acceptor may be optionally employed in the synthesis described above. Examples of suitable acid acceptors include, but are not limited to, potassium carbonate, sodium bicarbonate, triethylamine, pyridine, trimethylamine, and the like, and mixtures thereof.
Solvents (hydrocarbon and polar solvents) may be optionally employed in the synthesis of haloamines in accordance with the present invention. Suitable solvents include, but are not limited to, water, tetrahydrofuran, hexane, cyclohexane, toluene, acetonitrile, methyl-t-butyl ether, diethoxymethane, methanol, and the like and mixtures thereof.
In another aspect of the invention, processes for preparing tertiary aminoalkylorganometallic compounds are provided. Tertiary aminoalkylorganometallic compounds prepared in accordance with the present invention are represented generally by the formula R1R2Nxe2x80x94R3xe2x80x94M (II) (singly and mixtures thereof), wherein:
R1 and R2 are independently chiral or achiral and independently selected from the group consisting of hydrogen; saturated or unsaturated, linear or branched, C1 to C16 alkyl; saturated or unsaturated C3-C16 cycloalkyl; saturated or unsaturated, linear or branched, silyl-, amino- or oxy-substituted C1-C16 alkyl; saturated or unsaturated silyl-, amino- or oxy-substituted C3-C16 cycloalkyl; saturated or unsaturated, linear or branched, substituted C1-C16 alkyl containing saturated or unsaturated linear or branched C1 to C8 lower alkyl, C3-C16 cycloalkyl, C3-C10 aryl, or substituted aryl containing saturated or unsaturated linear or branched C1-C8 lower alkyl or C3-C8 cycloalkyl; saturated or unsaturated substituted C3-C16 cycloalkyl containing saturated or unsaturated linear or branched C1-C8 lower alkyl, C3-C8 cycloalkyl, C3-C10 aryl, or substituted aryl containing saturated or unsaturated linear or branched C1-C8 lower alkyl or C3-C8 cycloalkyl; or R1 and R2 together may represent a C4-C16 alkylene R4
which alkylene may be saturated or unsaturated, optionally substituted with silyl, amino, or oxygen, or optionally substituted with saturated or unsaturated linear or branched C1-C8 alkyl, C3-C8 cycloalkyl, C3-C10 aryl, or substituted aryl containing saturated or unsaturated linear or branched C1-C8 lower alkyl or C3-C8 cycloalkyl;
R3 is selected from the group consisting of saturated or unsaturated, linear or branched, C3-C25 alkyl; saturated or unsaturated C3-C25 cycloalkyl; saturated or unsaturated, linear or branched, substituted C3-C25 alkyl containing saturated or unsaturated linear or branched C1-C8 alkyl, C3-C8 cycloalkyl, C3-C10 aryl, or substituted aryl containing saturated or unsaturated linear or branched C1-C8 alkyl or C3-C8 cycloalkyl; saturated or unsaturated substituted C3-C25 cycloalkyl containing saturated or unsaturated linear or branched C1-C8 alkyl, C3-C8 cycloalkyl, C3-C10 aryl, or substituted aryl containing saturated or unsaturated linear or branched C1-C8 alkyl or C3-C8 cycloalkyl; and
M is an alkali metal, preferably lithium, and mixtures thereof.
The improved processes of the invention for preparing aminoalkylorganometallic compounds involves the reaction of selected tertiary haloalkylamines, such as described above of Formula I, singly and mixtures thereof, wherein the R3 group is a connecting or tether group which contains three to twenty-five carbon atoms, with an alkali metal selected from lithium, sodium and potassium, and mixtures thereof, at an elevated temperature ( greater than 45xc2x0 C.), in a hydrocarbon solvent containing five to ten carbon atoms and mixtures of such solvents to form alkylorganometallic compounds (singly and mixtures thereof) containing an amine, such as represented by Formula II above.
Examples of haloamines useful in the practice of this aspect of the invention include, but are not limited to, 3-(N,N-dimethylamino)-1-propyl halide, 3-(N,N-dimethylamino)-2-methyl-1-propyl halide, 3-(N,N-diethylamino)-2,2-dimethyl-1-propyl halide, 5-(N,N-dimethylamino)-1-pentyl halide, 4-(N-ethyl-N-methylamino)-1-butyl halide, 3-(piperidino)-1-propyl halide, 3-(pyrrolidino)-2-methyl-1-propyl halide, 6-(pyrrolidino)-1-hexyl halide, 3-(hexamethyleneimino)-1-propyl halide, 3-(hexamethyleneimino)-2,2-dimethyl-1-propyl halide, 4-(hexamethyleneimino)-2-butenyl-1-halide, 3-(1,4-diaza-4-methyl-1-cycloheptyl)-1-propyl halide, 4-(1,4-diaza-4-methyl-1-cycloheptyl)-1-butyl halide, 3-(N-isopropyl-N-methyl)-2-methyl-1-propyl halide, 3-(2,2,5,5-tetramethyl-2,5-disila-1-azacyclopentane)-1-propyl halide, 4-(2,2,5,5-tetramethyl-2,5-disila-1-azacyclopentane)-1-butyl halide, 6-(2,2,5,5-tetramethyl-2,5-disila-1-azacyclopentane)-1-hexyl halide, and the like, and mixtures thereof.
Examples of hydrocarbon solvents include, but are not limited to, cyclohexane, pentane, hexane, heptane, octane, cyclopentane, methylcyclohexane, toluene, ethylbenzene, cumene, and the like, and mixtures thereof.
The alkali metal used in preparing the aminoalkylorganometallic compounds containing amines of Formula II is selected from lithium, sodium and potassium, and preferably is used as a dispersion whose particle size usually does not exceed about 300 microns. Preferably the particle size is between 10 and 300 microns, although coarser particle size alkali metal can be used. When lithium is used, the lithium metal can contain 0.2 to 1.0, and preferably 0.8, weight percent sodium. The alkali metal is used in amounts of 90% of theoretical to a 400% excess above the theoretical amount necessary to produce the compounds of Formula II. The reaction temperature is greater than about 45xc2x0 C. up to just below the decomposition of the reactants and/or the product. An abrasive as known in the art can be optionally added to improve the metallation reaction. The yields of tertiary aminoalkylorganometallic compounds prepared by this invention typically exceed 90%.
Advantages of the elevated temperature process to prepare the tertiary aminoalkylorganometallic compounds include: higher yield of desired product; less Wurtz coupling by-product; less unreacted haloamino starting material; more consistent initiation; and less soluble lithium chloride by-product.
For example, the isolated yield of 3-(hexamethyleneimino)-1-propyllithium was 94.9% when it was prepared at elevated temperature (55-65xc2x0 C.). When the same aminoalkyllithium compound was prepared at 33-39xc2x0 C., the yield plummeted to 77.8%.
This aspect of the invention is illustrated, for example, by Equation 6:
Equation 6: 
The tertiary aminoalkylorganometallic compounds can have utility as initiators in anionic polymerization of conjugated dienes and alkenylsubstituted aromatic compounds. The resultant polymer, which contains a tertiary amino group, can exhibit improved characteristics, such as improved hysteresis loss characteristics.